去甲肾上腺素摄取到大鼠脑突触小泡中的立体选择性

Stereoselectivity of noradrenaline uptake into synaptic vesicles of the rat brain.

作者信息

Matthaei H, Pramono S, Philippu A

机构信息

Institut für Pharmakodynamik und Toxikologie, Universität Innsbruck, Austria.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):621-5. doi: 10.1007/BF00175786.

DOI:10.1007/BF00175786

PMID:3216895

Abstract

To investigate the stereoselectivity of the ATP-Mg2+-dependent uptake of noradrenaline, synaptic vesicles were isolated from the rat brain by differential centrifugation and incubated with 3H-(+/-)-, 3H-(-)- or 14C-(+)-noradrenaline in the absence and in the presence of ATP-Mg2+. The Km values of the ATP-Mg2+-dependent uptake were found to be different for the two isomers (mumol/l): 3H-(+/-)-noradrenaline 14.9 +/- 2.2 x 10(-1), 3H-(-)-noradrenaline 7.7 +/- 0.5 x 10(-1), 14C-(+)-noradrenaline 17.3 +/- 3.7 x 10(-1), whereas the Vmax of the racemate was identical with those of the two isomers (pmol/mg protein/min): 3H-(+/-)-noradrenaline 5.5 +/- 0.4, 3H-(-)-noradrenaline 4.9 +/- 0.1, 14C-(+)-noradrenaline 5.1 +/- 0.4. Moreover, (+)-noradrenaline inhibited competitively the ATP-Mg2+-dependent uptake of 3H-(+/-)-noradrenaline (Ki 19.2 +/- 1.0 x 10(-1) mumol/l) and 3H-(-)-noradrenaline (Ki 17.7 +/- 1.8 x 10(-1) mumol/l), the Ki values being nearly identical with the Km of the ATP-Mg2+-dependent uptake of 14C-(+)-noradrenaline. It is concluded that the ATP Mg2+-dependent uptake of noradrenaline into synaptic vesicles of the rat brain is stereoselective and that both isomers share the same transport system.

摘要

为研究去甲肾上腺素依赖ATP - Mg²⁺摄取的立体选择性，通过差速离心从大鼠脑分离突触小泡，并在不存在和存在ATP - Mg²⁺的情况下，将其与³H-(±)-、³H-(-)-或¹⁴C-(+)-去甲肾上腺素一起孵育。发现两种异构体的ATP - Mg²⁺依赖摄取的Km值不同（μmol/L）：³H-(±)-去甲肾上腺素为14.9±2.2×10⁻¹，³H-(-)-去甲肾上腺素为7.7±0.5×10⁻¹，¹⁴C-(+)-去甲肾上腺素为17.3±3.7×10⁻¹，而外消旋体的Vmax与两种异构体的相同（pmol/mg蛋白/分钟）：³H-(±)-去甲肾上腺素为5.5±0.4，³H-(-)-去甲肾上腺素为4.9±0.1，¹⁴C-(+)-去甲肾上腺素为5.1±0.4。此外，(+)-去甲肾上腺素竞争性抑制³H-(±)-去甲肾上腺素（Ki 19.2±1.0×10⁻¹ μmol/L）和³H-(-)-去甲肾上腺素（Ki 17.7±1.8×10⁻¹ μmol/L）的ATP - Mg²⁺依赖摄取，Ki值与¹⁴C-(+)-去甲肾上腺素的ATP - Mg²⁺依赖摄取的Km值几乎相同。结论是，大鼠脑突触小泡中去甲肾上腺素的ATP - Mg²⁺依赖摄取具有立体选择性，且两种异构体共享相同的转运系统。